Fasting is often used for obesity correction but the “refeeding syndrome” limits its efficiency, and molecular mechanisms underlying metabolic response to different food availability are under investigation. Sex was shown to affect hormonal and metabolic reactions to fasting/refeeding. The aim of this study was to evaluate hormonal and transcriptional responses to fasting and refeeding in male and female C57Bl/6J mice. Sex asymmetry was observed both at the hormonal and transcriptional levels. Fasting (24 h) induced increase in hepatic Fgf21 gene expression, which was associated with elevation of plasma FGF21 and adiponectin levels, and the upregulation of expression of hepatic (Pparα, Cpt1α) and muscle (Cpt1β, Ucp3) genes involved in fatty acid oxidation. These changes were more pronounced in females. Refeeding (6 h) evoked hyperinsulinemia and increased hepatic expression of gene related to lipogenesis (Fasn) only in males and hyperleptinemia and increase in Fgf21 gene expression in muscles and adipose tissues only in females. The results suggest that in mice, one of the molecular mechanisms underlying sex asymmetry in hepatic Pparα, Cpt1α, muscle Cpt1β, and Ucp3 expression during fasting is hepatic Fgf21 expression, and the reason for sex asymmetry in hepatic Fasn expression during refeeding is male-specific hyperinsulinemia.

Fucose, the terminal glycan of the intestinal glycoprotein Mucin2, was shown to have an anti-inflammatory effect in mouse colitis models and modulate immune response due to macrophage polarization changes. In this study we evaluated the effect of 0.05% L-fucose supplementation of drinking water on immune parameters in the intestine of homozygous mutant Muc2^−/−, compared to Muc2^+/+ mice. To get into innate and adaptive immunity mechanisms of gut inflammation, we tested Prkdc^SCIDMuc2^−/− strain, Muc2 knockout on SCID background, that is characterized by lack of lymphocytes, in comparison with Prkdc^SCID mice. We evaluated intestinal cytokine profiling, macrophage and eosinophil infiltration, and expression of Nos2 and Arg1 markers of macrophage activation in all strains. Markers of Th1, Treg and Th17 cells (Tbx21, Foxp3, and Rorc expression) were evaluated in Muc2^−/− and Muc2^+/+ mice. Both Muc2^−/− and Prkdc^SCIDMuc2^−/− mice demonstrated increased numbers of macrophages, eosinophils, elevated levels of TNFa, GM-CSF, and IL-10 cytokines. In Muc2^−/− mice we observed a wide range of pro-inflammatory cytokines elevated, such as IFN-gamma, IL-1b, IL-12p70, IL-6, M-CSF, G-CSF, IL-17, MCP-1, RANTES, MIP1b, MIP2. Muc2^−/− mice demonstrated increase of Nos2, Tbx21 and Foxp3 genes mRNA, while in Prkdc^SCIDMuc2^−/− mice Arg1 expression was increased. We found that in Muc2^−/− mice L-fucose reduced macrophage infiltration and IL-1a, TNFa, IFNgamma, IL-6, MCP-1, RANTES, MIP1b levels, decreased Nos2 expression, and induced the expression of Treg marker Foxp3 gene. On the contrary, in Prkdc^SCIDMuc2^−/− mice L-fucose had no effect on macrophage and eosinophil numbers, but increased TNFa, GM-CSF, IL-12p70, IL-6, IL-15, IL-10, MCP1, G-CSF, IL-3 levels and Nos2 gene expression, and decreased Arg1 gene expression. We demonstrated that anti-inflammatory effect of L-fucose observed in Muc2^−/− mice is not reproduced in Prkdc^SCIDMuc2^−/−, which lack lymphocytes. We conclude that activation of Treg cells is a key event that leads to resolution of inflammation upon L-fucose supplementation in Muc2^−/− mice.

Intestinal mucus protects epithelial and immune cells from the gut resident microorganisms, and provides growth-promoting factors as mucus-derived O-glycans for beneficial bacteria. A lack of intestinal protective mucus results in changes in the commensal microflora composition, mucosal immune system reprogramming, and inflammation. Previous work has shown that fucose, the terminal glycan chain component of the intestinal glycoprotein Mucin2, and fucoidan polysaccharides have an anti-inflammatory effect in some mouse models of colitis. This study evaluates the effect of fucose on reproductive performance in heterozygous mutant Muc2 female mice. We found that even though Muc2^+/− females are physiologically indistinguishable from C57Bl/6 mice, they have a significantly reduced reproductive performance upon dietary fucose supplementation. Metagenomic analysis reveals that the otherwise healthy wild-type siblings of Muc2^−/− animals have reduced numbers of some of the intestinal commensal bacterial species, compared to C57BL/6 mice. We propose that the changes in beneficial microflora affect the immune status in Muc2^+/− mice, which causes implantation impairment. In accordance with this hypothesis, we find that macrophage polarization during pregnancy is impaired in Muc2^+/− females upon addition of fucose. Metabolic profiling of peritoneal macrophages from Muc2^+/− females reveals their predisposition towards anaerobic glycolysis in favor of oxidative phosphorylation, compared to C57BL/6-derived cells. In vitro experiments on phagocytosis activity and mitochondrial respiration suggest that fucose affects oxidative phosphorylation in a genotype-specific manner, which might interfere with implantation depending on the initial status of macrophages. This hypothesis is further confirmed in BALB/c female mice, where fucose caused pregnancy loss and opposed implantation-associated M2 macrophage polarization. Taken together, these data suggest that intestinal microflora affects host immunity and pregnancy outcome. At the same time, dietary fucose might act as a differential regulator of macrophage polarization during implantation, depending on the immune status of the host.

У мышей с мутацией lethal yellow (A y ) фармакологические эффекты фактора роста фибробластов 21 зависят от пола

The article presents information on the methods and results of studying the influence of extracts prepared from various organs of the caper plant (Capparis spinosa L.), which in the Samarkand region exhibits the absence of proliferative activity of monocyte macrophages and mouse RAW 264.7. There are many scientific and research works devoted to the study of the medicinal properties of Capparis spinose L. cappers growing in Uzbekistan, as well as many works dedicated to identifying the molecular mechanisms of the immunomodulatory properties of the plant, which have not yet been studied. In medicine, consuming ripe fruits of C. spinosa L. has long been known to treat various diseases' inflammatory processes, including stomach inflammation and intestinal bleeding processes of haemorrhoids. The experiments show that concentrations of plant extracts at a concentration of 25.5 ?l have a destructive effect on all samples. A concentration of 1 ?l reduces the proliferative activity of cells of all plant extracts, except for seed extract; as a result, when exposed to 1 ?l of seed extraction, the population level was the highest. In cells stimulated with LPS, the level of proliferation was high at a concentration of 0.5 ?l of extracts of flowers, fruits and roots. Cytotoxicity was observed in extratax leaves, which may explain the antibacterial activity.

Fasting has become increasingly popular for treatment and prevention of obesity. Sex differences in the mechanisms of adaptation to fasting may contribute to choosing a therapeutic strategy for correction of metabolic disorders. Hepatokine fibroblast growth factor 21 (FGF21) is involved in the adaptation to fasting. Muscles are assumed to be the main energy-consuming tissue in the body, as muscle metabolism plays an important role in the adaptation to nutritional deficit. However, there is still little information on sex differences in muscle and FGF21 physiological response to fasting. Our aim was to find out whether there were sex differences in hormonal regulation and the expression of genes controlling glucose and lipid metabolism in skeletal muscles in response to fasting. We estimated the effect of 24-hour fasting on the expression of genes involved in lipid (Ucp3, Cpt1) and carbohydrate (Slc2a4) metabolism in muscles and evaluated changes in body weight and blood plasma levels of glucose, insulin, free fatty acids (FFA), adiponectin, and FGF21 in male and female C57BL/6J mice. None of the genes studied (Ucp3, Cpt1 and Slc2a4) showed sex-related changes at mRNA levels in control groups, but females exposed to fasting demonstrated a significant increase in the expression of all genes as compared to control. Fasting significantly decreased body weight and glucose blood plasma levels in animals of both sexes but exerted no effect on the levels of insulin or FFA. The adiponectin and FGF21 levels were increased in response to fasting, the increase in females being significant. We were first to show sex dimorphism in muscle gene expression and FGF21 blood level in response to fasting. In females, the greater increase in FGF21 and adiponectin blood levels was positively associated with the greater upregulation of lipid oxidation and glucose uptake gene expression.